Studies described in the progress report and those in progress, are related to the fundamental and clinical aspects of photochemotherapy of psoriasis with psoralens. Photochemotherapy defines the clinical use of electromagnetic radiation (320-400 nm UV-A) in combination with drug (methoxsalen or other photoactive psoralens) to bring about a beneficial effect. The molecular studies pertaining to the cross-linking of certain psoralens to DNA suggest that the photochemotherapeutic effectiveness of psoralens in psoriasis is closely related to their cross-linking ability with epidermal DNA and also to the degree of inhibition of DNA synthesis. The cross-linking of 8-methoxypsoralen to epidermal DNA is light-dependent and has been demonstrated both under in vitro and in vivo conditions. The kinetics and the action spectrum of this photoreaction are being investigated. The enzyme induction studies in mice and rats concerning the metabolism of therapeutically useful psoralens (8-methoxypsoralen and trimethylpsoralen) indicate that systemically administered psoralens which are potent skin photosensitizers can induce hepatic drug-metabolizing enzymes such as arylhydrocarbon hydroxylase, ethyl morphine N-demethylase, and cytochrome P450. Inactive or nonphotosensitizing psoralens have no effect on any of these enzymes of P450. These studies suggest the possibility that methoxsalen and other therapeutically useful drugs are metabolized by the mixed-function oxidase enzyme system in the liver. The kinetics of absorption and the metabolic biotransformation of orally administered psoralens (psoralen, 4,5',8-trimethylpsoralen, and 8-methoxypsoralen) have been examined in mice. New metabolites of trimethylpsoralen and 8-methoxypsoralen have been characterized and isolated from the urine of mice and men receiving oral psoralens. Studies related to the carcinogenic aspects of photochemotherapy (psoralen and UV-A) are in progress. Albino and pigmented mice are receiving methoxsalen by oral intubation (dose range 0.2 mg-25 mg/kg) and carcinogenic effects of UV-A radiation is being investigated.